About Enhancer
| Enhancer ID: | E_01_0412 |
| Species: | human |
| Position : | chr21:25877858-25879858   |
| Biosample name: | |
| Experiment class : | High+Lowthroughput |
| Enhancer type: | Enhancer |
| Disease: | Alzheimer's disease (ad) |
| Pubmed ID: | 29899688 |
| Enhancer experiment: | transgenic mice,qRT-PCR,SDS-PAGE,Western blot,Immunohistochemistry, |
| Enhancer experiment description: | To study the relationship between Mg2+ and TNF-?, we used human- or mouse-derived glial and neuronal cell lines or APP/PS1 transgenic (Tg) mice as in vitro and in vivo experimental models, respectively. Our data demonstrates that magnesium-L-threonate (MgT) can decrease the expression of TNF-? by restoring the levels of Mg2+ in glial cells. In addition, PI3-K/AKT and NF-?B signals play critical roles in mediating the effects of Mg2+ on suppressing the expression of TNF-?. In neurons, Mg2+ elevation showed similar suppressive effects on the expression of presenilin enhancer 2 (PEN2) and nicastrin (NCT) through a PI3-K/AKT and NF-?B-dependent mechanism. As the major components of ?-secretase, overexpression of presenilin 1 (PS1), PEN2 and NCT potentially promote the synthesis of A?, which in turn activates TNF-? in glial cells. Reciprocally, TNF-? stimulates the expression of PEN2 and NCT in neurons. The crosstalk between TNF-? and A? in glial cells and neurons could ultimately aggravate the development and progression of AD. |
About Target gene
| Target gene : | -- |
| Strong evidence: | qRT-PCR,qPCR,ChIP,3C |
| Less strong evidence: | RNA-Seq |
| Target gene experiment description: | To study the relationship between Mg2+ and TNF-?, we used human- or mouse-derived glial and neuronal cell lines or APP/PS1 transgenic (Tg) mice as in vitro and in vivo experimental models, respectively. Our data demonstrates that magnesium-L-threonate (MgT) can decrease the expression of TNF-? by restoring the levels of Mg2+ in glial cells. In addition, PI3-K/AKT and NF-?B signals play critical roles in mediating the effects of Mg2+ on suppressing the expression of TNF-?. In neurons, Mg2+ elevation showed similar suppressive effects on the expression of presenilin enhancer 2 (PEN2) and nicastrin (NCT) through a PI3-K/AKT and NF-?B-dependent mechanism. As the major components of ?-secretase, overexpression of presenilin 1 (PS1), PEN2 and NCT potentially promote the synthesis of A?, which in turn activates TNF-? in glial cells. Reciprocally, TNF-? stimulates the expression of PEN2 and NCT in neurons. The crosstalk between TNF-? and A? in glial cells and neurons could ultimately aggravate the development and progression of AD. |
About TF
| TF name : | APP |
| TF experiment: | transgenic mice,qRT-PCR,SDS-PAGE,Western blot,Immunohistochemistry, |
| TF experiment description: | To study the relationship between Mg2+ and TNF-?, we used human- or mouse-derived glial and neuronal cell lines or APP/PS1 transgenic (Tg) mice as in vitro and in vivo experimental models, respectively. Our data demonstrates that magnesium-L-threonate (MgT) can decrease the expression of TNF-? by restoring the levels of Mg2+ in glial cells. In addition, PI3-K/AKT and NF-?B signals play critical roles in mediating the effects of Mg2+ on suppressing the expression of TNF-?. In neurons, Mg2+ elevation showed similar suppressive effects on the expression of presenilin enhancer 2 (PEN2) and nicastrin (NCT) through a PI3-K/AKT and NF-?B-dependent mechanism. As the major components of ?-secretase, overexpression of presenilin 1 (PS1), PEN2 and NCT potentially promote the synthesis of A?, which in turn activates TNF-? in glial cells. Reciprocally, TNF-? stimulates the expression of PEN2 and NCT in neurons. The crosstalk between TNF-? and A? in glial cells and neurons could ultimately aggravate the development and progression of AD. |
About Function
| Enhancer function : | To study the relationship between Mg2+ and TNF-?, we used human- or mouse-derived glial and neuronal cell lines or APP/PS1 transgenic (Tg) mice as in vitro and in vivo experimental models, respectively. Our data demonstrates that magnesium-L-threonate (MgT) can decrease the expression of TNF-? by restoring the levels of Mg2+ in glial cells. In addition, PI3-K/AKT and NF-?B signals play critical roles in mediating the effects of Mg2+ on suppressing the expression of TNF-?. In neurons, Mg2+ elevation showed similar suppressive effects on the expression of presenilin enhancer 2 (PEN2) and nicastrin (NCT) through a PI3-K/AKT and NF-?B-dependent mechanism. As the major components of ?-secretase, overexpression of presenilin 1 (PS1), PEN2 and NCT potentially promote the synthesis of A?, which in turn activates TNF-? in glial cells. Reciprocally, TNF-? stimulates the expression of PEN2 and NCT in neurons. The crosstalk between TNF-? and A? in glial cells and neurons could ultimately aggravate the development and progression of AD. |
| Enhancer function experiment: | Immunohistochemical staining |
| Enhancer function experiment description: |
To study the relationship between Mg2+ and TNF-?, we used human- or mouse-derived glial and neuronal cell lines or APP/PS1 transgenic (Tg) mice as in vitro and in vivo experimental models, respectively. Our data demonstrates that magnesium-L-threonate (MgT) can decrease the expression of TNF-? by restoring the levels of Mg2+ in glial cells. In addition, PI3-K/AKT and NF-?B signals play critical roles in mediating the effects of Mg2+ on suppressing the expression of TNF-?. In neurons, Mg2+ elevation showed similar suppressive effects on the expression of presenilin enhancer 2 (PEN2) and nicastrin (NCT) through a PI3-K/AKT and NF-?B-dependent mechanism. As the major components of ?-secretase, overexpression of presenilin 1 (PS1), PEN2 and NCT potentially promote the synthesis of A?, which in turn activates TNF-? in glial cells. Reciprocally, TNF-? stimulates the expression of PEN2 and NCT in neurons. The crosstalk between TNF-? and A? in glial cells and neurons could ultimately aggravate the development and progression of AD. |
About SNP
| SNP ID: | -- |
Upstream Pathway Annotation of TF
Enhancer associated network
The number on yellow line represents the distance between enhancer and
target gene